In Patients Experiencing Pain and Inflammation, the Use of Non-Steroidal Anti-Inflammatory Drugs Is More Likely a Marker of the Observed Cardiovascular Risk Rather than Its Cause: A Viewpoint

Non-steroidal anti-inflammatory drugs (NSAIDs) have been among the most frequently prescribed medications worldwide for several decades. Ongoing vigilance regarding their potential adverse effects on the gastrointestinal tract and kidneys remains critical. Over the past twenty years, accumulating evidence has indicated an increased cardiovascular (CV) risk associated with NSAID use, posing a significant challenge for both patients and healthcare providers. This issue has prompted the US Food and Drug Administration (FDA) to issue explicit warnings concerning NSAID use. Recent data and comparative analyses of existing publications provide a basis for critically re-evaluating the association between NSAID use and potential CV risk, particularly when NSAIDs are administered for approved indications such as the treatment of pain and inflammation in patients with arthritis. The debate regarding the CV safety of NSAIDs centers on establishing causality. It is necessary to determine whether NSAIDs directly induce CV risks by initiating new pathological processes or act as modulators that influence the severity of pre-existing susceptibilities. The evidence presented in this review supports the view that NSAIDs do not create new CV risks but reduce CV incidents in patients with inflammatory pathologies such as arthritis. Conversely, NSAIDs have been observed to slightly increase CV risk when used at inappropriate high doses or in patients without inflammatory pain, such as those with Alzheimer's disease or other vulnerable populations. This perspective shifts the focus from causality to context-based risk management. The distinction between risk generation and risk modulation is proposed as a framework for the rational use of NSAIDs. The potential for NSAIDs to exacerbate pre-existing CV risk is dependent on the context of morbidity, and is low when used for anti-inflammatory indications in populations with the highest benefit, i.e., those with inflammatory morbidities. A general condemnation of NSAIDs keeps relevant patient populations from the only anti-inflammatory analgetic pharmacotherapy so far available.